Photochemical sterilization of blood products is the ultimate goal of this project, in which we are quantitating photochemical destruction of virus in blood and blood products and the effects of the process on the native blood components. Initial studies using an XeCl excimer laser characterized the response of virus and blood components as functions of cumulative fluence and peak irradiance. Single- and multiple-photon photochemical schemes were investigated. Single-photon photochemistry resulted in an efficacious treatment range between 10 and 20 J/sq cm, in which a hardy virus is inactivated and platelets and plasma proteins are minimally affected. Multiple-photon effects at higher irradiance led to increased protein damage in blood components, without increasing efficacy of viral inactivation. Augmentation of this therapeutic window by photochemistry (using exogenous agents such as riboflavin, tetracycline, and hemocyanin) was investigated, with a focus on the adverse effects on platelets and the relative susceptibility of different viruses, depending on the complexity of their coats. The inhibitory effect of serum albumin on photochemistry was also examined. Proposed work will examine exogenous agents that show strong affinity for binding to DNA, and thereby might increase therapeutic efficacy. The high sensitivity of blood platelets to activation and/or damage by photochemical products (e.g., singlet oxygen) has led to a renewed emphasis on optical and immunological methods of monitoring minimal lesions associated with viral inactivation photochemistry, as well as standard blood-banking techniques of preparation and storage.